Ryanodine receptor adaptation and Ca$^2+$(-)induced Ca$^2+$
release-dependent Ca$^2+$ oscillations.
Biophys. J., 71 (6):
3477--3487 (December 1996)Abstract
A simplified mechanism that mimics ädaptation" of the ryanodine receptor
(RyR) has been developed and its significance for Ca$^2+$(-)induced
Ca$^2+$ release and Ca$^2+$ oscillations investigated. For
parameters that reproduce experimental data for the RyR from cardiac
cells, adaptation of the RyR in combination with sarco/endoplasmic
reticulum Ca$^2+$ ATPase Ca$^2+$ pumps in the internal stores
can give rise to either low Cai2+ steady states or Ca$^2+$
oscillations coexisting with unphysiologically high Cai2+ steady
states. In this closed-cell-type model rapid, adaptation-dependent
Ca$^2+$ oscillations occur only in limited ranges of parameters.
In the presence of Ca$^2+$ influx and efflux from outside the
cell (open-cell model) Ca$^2+$ oscillations occur for a wide
range of physiological parameter values and have a period that is
determined by the rate of Ca$^2+$ refilling of the stores. Although
the rate of adaptation of the RyR has a role in determining the shape
and the period of the Ca$^2+$ spike, it is not essential for
their existence. This is in marked contrast with what is observed
for the inositol 1,4,5-trisphosphate receptor for which the biphasic
activation and inhibition of its activity by Ca$^2+$ are sufficient
to produce oscillations. Results for this model are compared with
those based on Ca$^2+$(-)induced Ca$^2+$ release alone in
the bullfrog sympathetic neuron. This kinetic model should be suitable
for analyzing phenomena associated with "Ca$^2+$ sparks," including
their merger into Ca$^2+$ waves in cardiac myocytes.
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